Opioids are any endogenous or exogenous compounds that bind to an opioid receptor. Opioid receptors are localized primarily in the brain, spinal cord, and gastrointestinal tract. There are four broad groups of opioids: endogenous opioid peptides produced in the body; naturally occurring opioid alkaloids such as morphine and codeine; semisynthetic opioids such as hydrocodone and oxycodone, and synthetic opioids such as fentanyl and methadone. When opioids bind to their receptors in the brain and spinal cord they block pain transmission signals from the periphery of the body. Although opioids are very effective for moderate to severe pain, there are many well known problems associated with opioid therapy. Those problems include serious side effects such as cognitive dysfunction, respiratory depression, nausea/vomiting, urinary retention, and constipation. Further, chronic opioid therapy often results in the development of tolerance to the analgesic effect (resulting in dose escalation) as well as physical and psychological dependence.
N-methyl-D-aspartate antagonists are known to be effective in suppressing the symptoms of opiate withdrawal. The anesthetic ketamine is the most potent N-methyl-D-aspartate antagonist available in clinical practice. See, for example, WO/2004/045601.
There is a great need for analgesic medications able to provide high efficacy pain relief while providing more favorable pharmacokinetics and reducing the possibility of undesirable effects. Therefore, there is a need for a way to administer opioids and norketamine to provide a more favorable and pharmacokinetic profile.